The controlling mechanisms which regulate production of inflammatory mediators by endotoxin stimulated murine macrophages are currently under investigation. Research has concentrated upon four important mediators; interferon, granulocytemacrophage colony stimulating factor (CSF), lymphocyte activating factor (LAF) and prostaglandins. Evidence obtained indicates that both prostaglandins and CSF may serve regulatory roles in mediator production by stimulated macrophages. E series prostaglandins (PGE) have been found to inhibit production of both CSF and interferon while CSF has been found to directly stimulate both PGE and LAF production by macrophages. Preliminary results suggest that CSF also sensitizes macrophages to endotoxin. CSF-cloned macrophages produced more interferon on a per cell basis than normal macrophages while normal macrophages preincubated with a source of CSF also responded in a hypersensitive manner. A partially purified CSF preparation has also been found to enhance LAF production by endotoxin-stimulated macrophages. Work in progress is designed to further investigate these oposing effects of PGE and CSF on macrophage functions.